NCT06520683

Adjuvant PD-1 Blockade for High-risk Stage-II DMMR/MSI-H Colorectal Cancer

Short-course PD-1 Blockade As Adjuvant Treatment for High-risk Stage-II DMMR/MSI-H Colorectal Cancer

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 180 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This open-label phase III trial investigates the efficacy of two cycles of PD-1 blockade (Tislelizumab) as adjuvant therapy to see how it works compared with standard of care (SOC) in treating patients with stage II dMMR/MSI-H colorectal cancer. The rational of giving PD-1 blockade as adjuvant therapy is based on the fact that tumor recurrence is extremely low among patients receiving neoadjuvant immunotherapy, which suggests that PD-1 blockade may likely improve patients' long-term survival. As for the short course (two cycles), we have the following considerations: firstly, the NICHE-2 trial, which adopted a two-cycle regimen, reported no recurrences during follow-up, suggesting that short-course anti-PD-1 therapy may be sufficient to improve the survival of patients with localized dMMR/MSI-H colorectal cancer. Secondly, the potential benefits of PD-1 blockade should be balanced against its toxicities, because patients with stage-II dMMR colorectal cancer generally have a good prognosis. Two cycles of PD-1 blockade have been shown to have a good safety profile, with low incidence of grade 3-4 and immune-related adverse events.

Detailed description

This is an open-label, multi-centre, randomised, phase III trial comparing the combination of PD-1 blockade + SOC versus SOC alone as adjuvant therapy for patients with high-risk stage-II dMMR/MSI-H colorectal cancer. Primary Objective: To determine whether the addition of Tislelizumab can significantly improve disease-free survival (DFS) compared to standard of care in patients with high-risk stage-II colorectal cancer. Secondary objectives: * To determine whether the addition of Tislelizumab can significantly improve overall survival (OS) compared to standard of care * To assess the adverse events (AE) profile (including immune-related adverse events, ir-AEs). OUTLINE: Patients are randomized to 1 of 2 arms, stratified by cT4 status. Arm 1 (experimental group): patients receive Tislelizumab 200mg intravenously on day 1, with or without adjuvant chemotherapy, and repeat the treatment on day 22. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5. Arm 2 (control group): patients receive standard of care (SOC), whether with surveillance alone, single-agent Capecitabine, or CapeOx/FOLFOX, at the discretion of the doctor in charge. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5. Statistics According to the statistical design, 180 patients (90 per arm) are to be randomized. The study is expected to take up to 36 months to complete accrual.

Conditions

• Colorectal Cancer
• Microsatellite Instability High

Interventions

Type	Name	Description
DRUG	Tislelizumab	\- Tislelizumab 200mg (day 1 and day 22), administered after surgery
DRUG	Adjuvant chemotherapy	* Adjuvant therapy is not mandatory. * Optional adjuvant regimens include FOLFOX, CapeOX, 5-FU+LV, or Capecitabine.

Timeline

• Start date: 2024-11-01
• Primary completion: 2027-11-01
• Completion: 2030-11-01
• First posted: 2024-07-25
• Last updated: 2024-11-07

Locations

1 site across 1 country: China